Formation of N-(glutathion-S-methylene)-4-aminoazobenzene following metabolic oxidation of the N-methyl group of the carcinogen, N-methyl-4-aminoazobenzene.
A major biliary metabolite of the hepatocarcinogen, N,N-dimethyl-4-aminoazobenzene (DAB), in the rat was identified as N-(glutathion-S-methylene)-4-aminoazobenzene (GS-CH2-AB). This conjugate was prepared synthetically by a Mannich condensation of 4-aminoazobenzene (AB), formaldehyde (CH2O) and glutathione (GSH) and has been characterized by chemical analysis and by ultraviolet, visible and 13C-NMR spectroscopy. The same conjugate was also formed in vitro by incubating N-methyl-4-aminoazobenzene (MAB), NADPH, NADH and GSH with rat hepatic microsomes. Evidence is presented that GSH reacted with an intermediate resulting from a cytochrome P-450-dependent oxidation of the N-methyl substituent. This reactive intermediate is presumed to be either an N-methylol or a methimine derivative of AB. The significance of this detoxification mechanism is discussed. The presence of an additional major aminoazo-dye GSH conjugate is also noted.
D000818:Animals; D001391:Azo Compounds / Q000378:metabolism*; D001646:Bile / Q000378:metabolism; D002273:Carcinogens / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D066298:In Vitro Techniques; D008658:Inactivation, Metabolic; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D010128:p-Aminoazobenzene / Q000031:analogs & derivatives / Q000378:metabolism*; D004124:p-Dimethylaminoazobenzene / Q000378:metabolism
D001391:Azo Compounds; D002273:Carcinogens; D010128:p-Aminoazobenzene; C005202:N-methyl-4-aminoazobenzene; C026707:3-(glutathion-S-yl)-N-methyl-4-aminoazobenzene; D004124:p-Dimethylaminoazobenzene; D005978:Glutathione